Endocrinology III Flashcards by Tim Agee

Where does Insulin act?

Muscle and fat

GLUT4 transporters

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T/F

Insulin inhibits lipolysis

True

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What becomes dominant when insulin decreases?

Glucagon - liver

Epinepherine - muscle

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Why can’t insulin be given orally?

Peptide hormone

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Type I diabetes is due to insulin _______.

Type II diabetes is due to insulin _______.

Deficiency

Resistance

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What 3 requirements are there for a random plasma glucose Diabetes diagnosis?

Glucose > 200 mg/dl
polyuria
polydipsia

(and/or weight loss)

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Why is there still high blood glucose in a diabetic in the fasting state?

There’s not enough insulin to get glucose from GNG and glycogenolysis into the cell.

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Hemoglobin A1c glucose level above _____ suggests diabetes.

6.5%

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T/F

Pre-diabetes always progresses to diabetes.

False

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Define:
polyuria
polydipsia
polyphagia

(excessive)
urination
thirst
food intake

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What contributes to diabetic hyperglycemia in the intestine and the kidney?

Intestine: decreases GLP-1
Kidney: SGLT-2 (glc transporter) over-expressed

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What are some tests to confirm Type I diabetes?

GAD (glutamic acid decarboxylase antibody)

ICA (islet cell cytoplasmic autoantibodies)

*GAD long-lasting

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There are many environmental factors leading to Type II diabetes. What are the 2 most important?

Obesity

Aging

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What most often breaks in type II Diabetes?

Post-receptor actions

pre-receptor is rare and receptor defects not often

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Ketones suggest…

Type I

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What is a non-insulin treatment for Type II diabetes that decreases liver glc production and fasting glc?

Biguanide

metformin

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What is an effective therapy for diabetes that stimulates beta cells, inhibits alpha cells, and decreases appetite?

Incretins

GLP-1

*expensive and effective

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What do SGL2T2 inhibitors do?

inhibit excretion of glc

*newest drugs

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What are the 2 background insulins?

long lasting, no peak

Glargine and Detemir

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What does it mean if blood glucose is high before a meal in a diabetic?

The previous meal wasn’t covered enough by insulin

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What can too much insulin cause?

Hypoglycemia
loss of consciousness
death

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What are 2 hormonal causes of hypoglycemia?

GH or Cortisol deficiency

*these cause insulin resistance. With no insulin resistance, glucose is taken up by muscle and fat and not enough for the brain

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What is a better treatment than snickers for hypoglycemia?

Glucagon injection

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What leads to lipolysis in type I diabetes?

unopposed Glucagon

*ketoacidosis

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What enzyme, suppressed by insulin, is over-active in response to epinephrine in type I diabetics?

Hormone Sensitive Lipase *fat pours out of adipose tissue=ketoacidosis

Why does ketoacidosis not occur in Type 2 diabetes?

insulin deficient but not completely absent

What does high blood glucose, high urine glucose, and salt/water loss lead to?

Dehydration and High Serum Osmolality

What happens to tissues freely permeable to glucose in long-term diabetes?

They break down Microangiopathies (retinopathy, neuropathy, nephropathy) Macroangiopathy (cerebral, coronary, peripheral)

What are AGE's?

Advanced Glycation Endproducts *highly reactive consequence of too much glc free radicals , cross linked proteins, etc.

What is ischemia?

Low oxygen to tissues | consequence of chronic hyperglycemia

What reduces inflammation in treatment for diabetic retinopathy?

Glucocorticoid

What risk factor goes way up in diabetic nephropathy?

heart disease | mortality 20-40 times higher

What is the mechanism of the slowed neural conduction in diabetic neuropathy?

semental demyelination *distal first - which is why problems with feet

What are the conditions that comprise metabolic syndrome? | need 3 of these

``` Hyperinsulinemia Hyperglycemia Hypertriglyceridemia Low HDL cholesterol Hypertension Central obesity ```

What causes foot problems in diabetics?

Loss of feeling Poor blood supply Poor wound healing (combined microvascular neuropathy and macrovascular disease)

Does intensive treatment of type I diabetes slow the onset of progression of disease?

Yes *bigtime

Does intensive glucose control prevent macrovascular complications in Type II diabetes?

No. *macrovascular disease outcomes the same

What two factors, if controlled, can benefit type II diabetes?

Blood pressure and Lipid control

How often should the feet be examined with a Diabetic patient? What common drug can be useful in preventing other complications?

Daily Aspirin

What do Leydig cells do?

Produce testosterone in presence of LH *in testes

What is the function of Sertoli cells?

secrete mullerian inhibiting substance "nurse" spermatogenisis process

When do gonads differentiate?

6 weeks

Describe the differentiation process at about 7 weeks.

Testosterone stimulates Wolffian ducts Mullerian inhibiting substance degenerates Female (mullerian) ducts

What do the formation of the penis, scrotum, and prostate require? What enzyme is involved?

DHT - dihydrotestosterone 5-alpha-reductase *undervirillization usually defect in process (usually amount of DHT)

review: | Male gonad feedback loops

GnRH > LH/FSH > Testosterone

What stimulates the testes to make testosterone before and after 12 weeks?

Before 12 weeks: HCG (human chorionic gonadotropin) from placenta After 12 weeks: FSH/LH from fetal pituitary

What does micropenis suggest?

Fetal pituitary failure * low LH = low testosterone = low DHT = micropenis * *must screen for other pituitary deficiencies

Testosterone effects the development of the ______ genitalia and dihydrotestosterone effects the development of the _____ genitalia.

Internal (vas defrens, etc) | External (scrotum, prostate, etc)

What does the maintenance of testicular germinal structures depend on?

Local testosterone | intra-testicular

What hormone stimulates the testes to produce testosterone?

How are GnRH and LH/FSH secreted?

pulses

What type of cells are stimulated by LH? FSH? (in men)

LH - Leydig cells (testosterone) (this diffuses to Sertoli cells) FSH - Sertoli cells (Inhibin B) *androgen binding protein

GnRH > | complete feedback

LH > Leydig cells > Testosterone FSH > Sertoli cells > Inhibin

What can convert testosterone to estradiol?

Aromatase | found mostly in fat

What is the abnormal migration of GnRH-producing neurons and (bundled with) olfactory neurons called?

Kallman syndrome *hypogonadism and no sense of smell

How are tertiary (hypothalamic) defects in sex hormones treated?

At primary level with testosterone | if fertility is the issue requires FSH/LH or GnRH via pump

HCG act in place of...

If there is trouble at the testes what are hormone levels?

high GnRH, FSH, LH low Testosterone

If someone is born without testes, what is the external genitalia?

female (internal and external)

When do testes fail in Klinefelter Syndrome?

After puberty

What are some target tissue defects in sexual differentiation?

Defective androgen receptor, 5-alpha-reductase (no DHT), aromatase (no estrogen)

If the testes are present but there are defective androgen receptors what would the hormone levels be?

high GnRH, FSH/LH, Testosterone, DHT, Estrogen

Why would androgen insensitivity syndrome produce no internal male or female genitalia?

Testosterone has no effect to produce male genitalia Mullerian inhibiting hormone gets rid of internal female genitalia

Androgens refer to what 2 molecules?

Testosterone and DHT

What are the hormone levels in 5-alpha-reductase deficiency?

Normal everything. *internal genitalia male, external female until puberty

What causes gynecomastia (excess breast tissue in males)?

excess Estrogen (E/T ration high) *common in aging

What condition includes the following: tall, epiphyses not closed, osteoporosis, normal genitalia, and abnormal semen?

``` No aromatase (so no estrogen) No estrogen receptors ```

Why would a continuous GnRH treatment be appropriate for prostate cancer?

GnRH that NOT in pulses down-regulates FSH and LH receptors also, 5-alpha reductase inhibitors (no DHT) is a treatment for prostate cancer

What developmental indicators are affected by hormones?

height | length at birth, bone growth

Is brain size (head circumference) affected by hormones?

NO *genetics, nutrition, environment

What 3 hormones affect length before birth?

insulin IGF-1 IGF-2

T/F | Endocrine causes of childhood obesity is common

False 0.1%

T/F | Height after birth isn't affected by hormones

FALSE *GH and IGF-1

Describe the growth feedback loop

GHRH > GH > IGF-1

What does thyroid hormone do developmentally?

Height (acts in concert with GH) Full fetal/child brain development

What are the 4 main hormones for growth?

GH IGF-1 Thyroid hormone Estrogen/testosterone (added at puberty) *remember - estrogen closes epiphyses

What are some endocrine causes of short stature?

hypothyroidism abnormal GH secretion excess Cortisol Precocious puberty

Thyroid hormone and GH both affect ____ more than _____.

height | weight

What effect does GH deficiency have on teeth?

gaps | small mandible

What does GH excess cause?

Gigantism or acromegaly

What is the difference between central and peripheral precocious puberty?

early puberty brought on by increases GnRH in Central brought on by abnormal hormone source in Peripheral

How is central precocious puberty treated? peripheral?

continuous GnRH treat underlying cause

T/F | Hypothyroidism and GH deficiency can present similarly.

True *fatigue, no growth in height, slow pulse, delayed deep tendon relaxation